title: Amelioration of epidermolysis bullosa by transfer of wild-type bone marrow cells.
abstract: The recessive dystrophic form of epidermolysis bullosa (RDEB) is a disorder of incurable skin fragility and blistering caused by mutations in the type VII collagen gene (Col7a1). The absence of type VII collagen production leads to the loss of adhesion at the basement membrane zone due to the absence of anchoring fibrils, which are composed of type VII collagen. We report that wild-type, congenic bone marrow cells homed to damaged skin, produced type VII collagen protein and anchoring fibrils, ameliorated skin fragility, and reduced lethality in the murine model of RDEB generated by targeted Col7a1 disruption. These data provide the first evidence that a population of marrow cells can correct the basement membrane zone defect found in mice with RDEB and offer a potentially valuable approach for treatment of human RDEB and other extracellular matrix disorders.
authors.affiliation: Blood and Marrow Transplantation Program, University of Minnesota, Minneapolis, MN 55455, USA. tolar003@umn.edu
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.forename: Akemi
authors.initials: A
authors.lastname: Ishida-Yamamoto
authors.forename: Megan
authors.initials: M
authors.lastname: Riddle
authors.forename: Ron T
authors.initials: RT
authors.lastname: McElmurry
authors.forename: Mark
authors.initials: M
authors.lastname: Osborn
authors.forename: Lily
authors.initials: L
authors.lastname: Xia
authors.forename: Troy
authors.initials: T
authors.lastname: Lund
authors.forename: Catherine
authors.initials: C
authors.lastname: Slattery
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism* / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D024143:Collagen Type VII / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation
chemical_list: D024143:Collagen Type VII